Modification of radiation responses of tissue by colchicine. Effects on mouse hair roots.

Abstract

Several recent reviews have described the effects of various chemical and physical agents in modifying radiation responses in normal tissues and tumors (1–3) . The observation that irradiation induces profound morphologic changes in animal and human hairs (4, 5) has provided a useful experimental device for the screening of such agents in rodents (6). At any given time areas of skin in rats and mice can be found in which most of the hair follicles are in the resting phase of the hair cycle. These telogen hair follicles are mitotically inactive and are insensitive to radiation (4). If the resting hair is disturbed by plucking, its follicle becomes active and a growing (anagen) hair is formed which is highly radiosensitive. When anagen hairs are irradiated, dysplastic changes in the shafts and atrophy of the bulbs occur, the number of hairs affected being proportionate to the dose of radiation sustained. Recent experiments in rats and mice have shown that anagen hairs also undergo profound atrophic and dysplastic changes following intraperitoneal administration of large doses of colchicine (7). Since these microscopic changes strongly resemble alterations in human hair induced by x-ray irradiation (5), the rodent hair indicator system was utilized to determine the possible synergistic role played by colchicine in increasing these x-ray effects. Our chief interest centered on the application of positive findings to the therapeutic implications of altering the radiosensitivity of certain forms of malignant growth by prior administration of colchicine. Methods The studies were carried out on adult female mice of the Carworth Farms No.1 strain. In these animals the hair cycle lasts for seventeen to twenty days from earliest anagen to the onset of telogen. Hairs were completely plucked from both haunches of all animals at the start of each experiment, one haunch being used for examination of the effects of colchicine and irradiation, and the other for examination of colchicine effects alone (Fig. 1). Occasional mice showing areas of newly growing hairs which were not easily removed were discarded from the study. The mice received x-ray irradiation on the tenth day after initial plucking, and four days later the newly growing hairs in the control and treatment areas were plucked. These hairs were then floated on a shallow layer of water covering the bottom of a 5.5 × 1.5 cm. glass Petri dish which had been scored in grid pattern on its underside. The hairs were examined with a binocular dissecting microscope at 45 × magnification with transmitted blue light. For each animal the following stages of hair growth were recorded and counted for the “differential hair count”: normal anagen, dysplastic, catagen (hairs transitional between anagen and telogen), and telogen (Fig. 2).